The objectives of this project are to understand the normal biology of human spermatozoa in the female reproductive tract and to be able to recognize alterations in semen quality and sperm function which indicate infertility. We have approached these objectives by study of individual sperm from carefully selected fertile and infertile men. We have developed new methodologies for assessment of human male fertility and we now have some insight into the pathophysiology of the human sperm cells. In the continuation of this project we will study in detail the biology of human sperm-zona pellucida interaction following sperm capacitation in vitro and in vivo (sperm recovered from the cervical canal). Zona binding inhibition studies with various saccharides will be carried out to study the nature of the sperm-zona bond. Lectin binding studies will be used to examine sperm surface changes which may be associated with zona binding. The ultrastructure of sperm-zona nellucida interaction will be studied as will the flagellar movement of spermatozoa on the zona surface. Parallel studies will be carried out with zona-free hamster oocytes to better understand the biology of human sperm interaction with the oolemma. The knowledge and methodology developed in these studies of normal biology will be applied in studies of infertile men to better understand the abnormalities of sperm cells which may lead to fertilization dysfunction. The efficacy of our previously developed diagnostic methodologies for objective assessment of human sperm motility and morphology will be evaluated in retrospective studies of infertility cases in which they have been applied. The statistical method of survival analysis will be applied to these data to calculate the probability of male fertility potential from the parameters of semen quality. A new diagnostic method for morphometric evaluation of human spermatozoa will be developed and applied to the assessment of human male infertility. The contribution of sub-fertile males to peri-implantation spontaneous abortion will be assessed by study of hCG and steroid conjugates in daily morning urine samples from their wives. The equipment, personnel and clinical resources have been assembled for a comprehensive, scientifically-sound study of the physiology and pathology of human spermatozoa. The continuation of this project will represent a long-term commitment to this goal.